Experimental Study On Adaption To Intrahepatic Cholestasis Induced By Rifampicin In Rats

Background: The drug-induced liver injury is the focus of clinical attention, it is notonly related to the patient’s life, but also may be an occupational risks for clinicians.Drug-induced liver injury has increasingly attracted the attention of doctors, but theadaptation to drug-induced liver injury is still difficult to understand and identify, whichis deserved special attention. Due to the requirements of medical ethics, we need to finda suitable animal model for research.Aims： Aims to observe adaption to liver injury induced by rifampicin and it’s dynamicchanges by detecting the activity of serum transaminases, bilirubin levels, liver tissue oxidation,histopathological and ultrastructural changes.Methods: Thirty-six male Wistar rats were randomly divided into normal controlgroup and rifampicin model group, treated with0.9%sodium chloride10ml/(kg d) andrifampicin100mg/(kg d) respectively by intragastric administration on an emptystomach. Serum alanine aminotransferase (ALT), aspartate aminotrans-ferase (AST) andTBIL,DBIL,ALP were estimated on d0,7,14,21,28,35,42and49in all the rats. Therats were sacrificed on14th day and49th day．Part of the liver tissue were made into10%liver homogenate.The content of TBA and MDA as well as the activities of GPxand SOD were measured in the liver homogenates.Histological analysis andultramicrostrcture of hepatocytes were carried out to assess the injury of the liver.Results:1. The rifampicin and control group rats were all alive before the end of study.In the process of animal experiments, the fur of rifampicin model group rats weredull,the feet and tail were obvious orange dye（Figure1）. The rifampicin and controlgroup rats were all alive before the end of study.In the process of animal experiments,the fur of rifampicin model group rats were dull,the feet and tail were obvious orangedye（Figure1）.The degree of jaundice were lower than before in the49th day.The liver/body weight ratio of rifampicin model rats were higher than the normal control groupin the49th day,the difference was statistically significant (P <0.01).2.Compared with normal control group, serum ALT,AST,TBIL,DBIL andALP in rifampicin group were obviously elevated（P＜0.05），and reached the peak atthe7th day to14th day, and then decreased slowly.3. Hepatic histology showed a steatosis associated with mild necrosis andinflammation in rifampicin model group. While liver cell ultrastructure showed localswelling of the mitochondria, fuzziness of rough endoplasmic reticulum, dilatation ofthe capillary bile duct with cholestasis.4.The level of TBA in liver tissue was also significantly increased（P＜0.01），Compared with normal control group, only liver tissues homogenate MDA inrifampicin group was significantly increased，simultaneously with decrease on livertissues homogenates SOD，GSH-PX also（P＜0.05）．Conclusions: Rifampicin can cause cholestatic liver damage, and exist adaption to liver injury...